Our central aim is to understand the interactions which take place between antigen molecules and lymphoid cells and which lead to the induction of immune phenomena, particularly antibody formation, under some circumstances and to a state of specific immunological tolerance under others. This broad umbrella covers most of the many on-going projects that have been part of this programme for the last fifteen years. In particular, five streams of activity are of present interest: 1. The induction of antibody formation in vitro. Here extensive use will be made of the congenitally athymic (nude) mouse in an effort to understand the relative roles of T cells, B cells and macrophages. 2. Critical testing of the clonal abortion theory of immunological tolerance. Here we will attempt to demonstrate and understand the exquisite capacity of differentiating (immature) B lymphocytes in the mouse bone marrow to be rendered tolerant by small concentrations of soluble antigens. 3. The induction of various types of B cell tolerance in mature B cells using hapten protein conjugates. 4. New methods of preparing hapten-specific B cells in highly enriched form from both virgin and pre-immunized spleen, and in a manner that allows them to react to antigen in tissue culture in an enriched way. 5. Techniques for studying the cellular distribution of I-associated antigens, and for their biochemical analysis.